title: Treatment efficacy and immune stimulation by AdCD40L gene therapy of spontaneous canine malignant melanoma.
abstract: Malignant melanoma is a serious disease in both humans and dogs, and the high metastatic potential results in poor prognosis for many patients. Its similarities with human melanoma make spontaneous canine melanoma an excellent model for comparative studies of novel therapies and tumor biology. We report a pilot study of local adenovector CD40L (AdCD40L) immunogene treatment in 19 cases of canine melanoma (14 oral, 4 cutaneous, and 1 conjunctival). Three patients were World Health Organization stage I, 2 were stage II, 10 stage III, and 4 stage IV. One to 6 intratumoral injections of AdCD40L were given every 7 days, followed by cytoreductive surgery in 9 cases and only immunotherapy in 10 cases. Tumor tissue was infiltrated with T and B lymphocytes after treatment, suggesting immune stimulation. The best overall response included 5 complete responses, 8 partial responses, and 4 stable and 2 progressive disease statuses according to the World Health Organization response criteria. Median survival was 160 days (range, 20-1141 d), with 3 dogs still alive at submission. Our results suggest that local AdCD40L therapy is safe and could have beneficial effects in dogs, supporting further treatment development. Clinical translation to human patients is in progress.
authors.affiliation: University Animal Hospital, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden. sara.westberg@uds.slu.se
authors.forename: Sara
authors.initials: S
authors.lastname: Westberg
authors.forename: Arian
authors.initials: A
authors.lastname: Sadeghi
authors.forename: Emma
authors.initials: E
authors.lastname: Svensson
authors.forename: Thomas
authors.initials: T
authors.lastname: Segall
authors.forename: Maria
authors.initials: M
authors.lastname: Dimopoulou
authors.forename: Olle
authors.initials: O
authors.lastname: Korsgren
authors.forename: Akseli
authors.initials: A
authors.lastname: Hemminki
authors.forename: Angelica S I
authors.initials: AS
authors.lastname: Loskog
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Tötterman
authors.forename: Henrik
authors.initials: H
authors.lastname: von Euler
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D023201:CD40 Ligand / Q000235:genetics* / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004285:Dogs; D005260:Female; D015316:Genetic Therapy / Q000009:adverse effects; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D010865:Pilot Projects
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016207:Cytokines; D023201:CD40 Ligand